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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #147046
Title: ENHANCED ANIMAL GROWTH VIA LIGAND-REGULATED GHRH MYOGENIC-INJECTABLE VECTORS

Author
item DRAGHIA-AKLI, RUXANDRA - BAYLOR COLLEGE MED
item MALONE, BRANDON - BAYLOR COLLEGE MED
item HILL, LEIGH - BAYLOR COLLEGE MED
item ELLIS, KENNETH - BAYLOR COLLEGE MED
item Schwartz, Robert
item NORDSTROM, JEFFREY - VALENTIS, INC.

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/14/2002
Publication Date: 3/1/2002
Citation: Draghia-Akli, R., Malone, P.B., Hill, L.A., Ellis, K.M., Schwartz, R.J., Nordstrom, J.L. 2002. Enhanced animal growth via ligand-regulated GHRH myogenic-injectable vectors. Federation of American Societies for Experimental Biology Journal. 16(3):426-8.

Interpretive Summary: We developed new biotechnology that will allow us to switch on and off growth in animals injected with a GHRH myogenic injectable DNA vectors with a simple oral inducible drug, mifepristone. The injected gene switch system is nontransgenic and can not be inherited. Normally the gene GHRH is off , but is induced with a non-natural steroid. We observed increased growth mediated through the enhanced IGF-I secretion , when mifepristone was given to mice.

Technical Abstract: Regulated animal growth occurred following a single electroporated injection of a mixture of two plasmids (10 microg of DNA), one expressing the GeneSwitch regulator protein, the other an inducible growth hormone releasing hormone (GHRH) gene, into the tibialis anterior muscles of adult SCID mice. Administration of the ligand mifepristone (MFP) up-regulated GHRH expression, as shown by elevations of IGF-I levels, and when MFP dosing was withdrawn, IGF-I returned to baseline levels. Five cycles of IGF-I induction were observed during a five-month period. Chronic MFP dosing for 25 days increased lean body mass, weight gain, and bone mineral density significantly compared with non-MFP treated controls. In summary, long-term drug-regulated GHRH expression was achieved following plasmid-based gene therapy, and chronic induction of GHRH expression in adult animals led to improvements in weight gain and body composition.